The purpose of this proposal is to investigate the interaction of arterial smooth muscle cells with the fish-oil class of fatty acids. Smooth muscle cells play a central role in the development of the atherosclerotic lesion. Early in the disease process, arterial smooth muscle cells become activated and migrate into the intima, where they accumulate lipid and contribute to the formation of the connective tissue matrix. The hypothesis to be tested is that exposure to and enrichment with the fish-oil fatty acids modulates the responsiveness of arterial smooth muscle cells, reducing their tendency to respond to activating factors and proliferate. All of the studies will be done with cultured smooth muscle cells. Four questions will be examined: (1) How are the fish oil (n-3) fatty acids handled by smooth muscle cells and is this different from the corresponding plant polyunsaturated fatty acids (n-6)? (2) To what extent can the lipids of smooth muscle cells become enriched with the fish oil polyunsaturates, and what factors regulate this process? (3) Does exposure to or enrichment with fish oil fatty acids affect the type of eicosanoids formed by smooth muscle cells or their capacity to respond to eicosanoids? (4) Will enrichment with fish oil fatty acids reduce the capacity of smooth muscle cells to become activated or their susceptability to injury?